122200-62-8Relevant articles and documents
Cyclooctatetraene: A Bioactive Cubane Paradigm Complement
Xing, Hui,Houston, Sevan D.,Chen, Xuejie,Ghassabian, Sussan,Fahrenhorst-Jones, Tyler,Kuo, Andy,Murray, Cody-Ellen P.,Conn, Kyna-Anne,Jaeschke, Kara N.,Jin, Da-Yun,Pasay, Cielo,Bernhardt, Paul V.,Burns, Jed M.,Tsanaktsidis, John,Savage, G. Paul,Boyle, Glen M.,De Voss, James J.,McCarthy, James,Walter, Gimme H.,Burne, Thomas H. J.,Smith, Maree T.,Tie, Jian-Ke,Williams, Craig M.
supporting information, p. 2729 - 2734 (2019/02/03)
Cubane was recently validated as a phenyl ring (bio)isostere, but highly strained caged carbocyclic systems lack π character, which is often critical for mediating key biological interactions. This electronic property restriction associated with cubane has been addressed herein with cyclooctatetraene (COT), using known pharmaceutical and agrochemical compounds as templates. COT either outperformed or matched cubane in multiple cases suggesting that versatile complementarity exists between the two systems for enhanced bioactive molecule discovery.
Cyclooctatetraenes through Valence Isomerization of Cubanes: Scope and Limitations
Houston, Sevan D.,Xing, Hui,Bernhardt, Paul V.,Vanden Berg, Timothy J.,Tsanaktsidis, John,Savage, G. Paul,Williams, Craig M.
supporting information, p. 2735 - 2739 (2019/02/07)
The scope and limitations of Eaton's rhodium(I)-catalyzed valence isomerization of cubane to cyclooctatetraene (COT) were investigated in the context of functional group tolerability, multiple substitution modes and the ability of cubane-alcohols to undergo one-pot tandem Ley–Griffith Wittig reactions in the absence of a transition metal catalyst.
Validating Eaton's Hypothesis: Cubane as a Benzene Bioisostere
Chalmers, Benjamin A.,Xing, Hui,Houston, Sevan,Clark, Charlotte,Ghassabian, Sussan,Kuo, Andy,Cao, Benjamin,Reitsma, Andrea,Murray, Cody-Ellen P.,Stok, Jeanette E.,Boyle, Glen M.,Pierce, Carly J.,Littler, Stuart W.,Winkler, David A.,Bernhardt, Paul V.,Pasay, Cielo,De Voss, James J.,McCarthy, James,Parsons, Peter G.,Walter, Gimme H.,Smith, Maree T.,Cooper, Helen M.,Nilsson, Susan K.,Tsanaktsidis, John,Savage, G. Paul,Williams, Craig M.
supporting information, p. 3580 - 3585 (2016/03/23)
Pharmaceutical and agrochemical discovery programs are under considerable pressure to meet increasing global demand and thus require constant innovation. Classical hydrocarbon scaffolds have long assisted in bringing new molecules to the market place, but an obvious omission is that of the Platonic solid cubane. Eaton, however, suggested that this molecule has the potential to act as a benzene bioisostere. Herein, we report the validation of Eaton's hypothesis with cubane derivatives of five molecules that are used clinically or as agrochemicals. Two cubane analogues showed increased bioactivity compared to their benzene counterparts whereas two further analogues displayed equal bioactivity, and the fifth one demonstrated only partial efficacy. Ramifications from this study are best realized by reflecting on the number of bioactive molecules that contain a benzene ring. Substitution with the cubane scaffold where possible could revitalize these systems, and thus expedite much needed lead candidate identification.
Cubanecarboxylic acids. Crystal engineering considerations and the role of C-H...O hydrogen bonds in determining O-H...Onetworks
Kuduva, Srinivasan S.,Craig, Donald C.,Nangia, Ashwini,Desiraju, Gautam R.
, p. 1936 - 1944 (2007/10/03)
A family of 4-substituted-1-cubanecarboxylic acids have been synthesized and their X-ray crystal structures analyzed. The rare syn-anti O-H...O catemer 6 is a recurring pattern in this series of compounds. Catemer 6 is observed in the crystal structures o
The cubane cage - A sensible probe for substituent effects on a four-membered ring
Irngartinger, Hermann,Strack, Stefan,Gredel, Frank
, p. 311 - 315 (2007/10/03)
The crystals of methyl 4-fluoro-1-cubanecarboxylate (1), methyl 4-chloro-1-cubanecarboxylate (2) and methyl cubanecarboxylate (5) are isomorphous to each other as are the crystals of methyl 4-bromo-1-cubanecarboxylate (3) and methyl 4-iodo-1-cubanecarboxylate (4). As a result of the space groups P21/m and Pnma, respectively, all molecules lie in a crystallographic mirror plane. Therefore, the methoxycarbonyl group is exactly planar, and the carbonyl fragment is in an eclipsed position to the cubane skeletal bond C2-C7. The electronic effects of the halogen atoms, in particular fluorine and chlorine, give rise to a shortening of the vicinal skeletal bonds. In contrast, the methoxycarbonyl groups causes a lengthening of the vicinal skeletal bonds C2-C6 and C2-C6A which are not in an eclipsed conformation. Ab initio calculations at the 6-31G* level of compounds 1, 2, and 5 confirm the experimental results. VCH Verlagsgesellschaft mbH, 1996.
Synthesis of Bridgehead Fluorides by Fluorodeiodination
Della, Ernest W.,Head, Nicholas J.
, p. 2850 - 2855 (2007/10/02)
Fluorodeiodination is found to be an attractive procedure for the synthesis of bridgehead fluorides.Thus, treatment of the corresponding iodide with xenon difluoride in dichloromethane at ambient temperature generally leads to high yields of the fluoride.Evidence suggests the intermediacy of the bridgehead cation in this reaction, and accordingly the substrates which are unfavorable disposed to fluorodeiodination are the bicycloalkyl iodides.In this context the isolation of a small quantity of methyl 4-fluorobicyclohexane-1-carboxylate (46, R= COOMe) is significant because it represents the first occasion on which the elusive 1-bicyclohexyl cation has been trapped.We have also demonstrated that synthesis of the iodides themselves can be accomplished efficiently both by Barton halodecarboxylation and by treatment of the carboxylic acid with lead tetraacetate and iodine.
Functionalization of Cubanes and Homocubanes via Oxidative Displacement of Iodine Using Hypervalent Iodine
Moriarty, Robert M.,Khosrowshahi, Jaffar S.
, p. 1395 - 1404 (2007/10/02)
The iodo group in 4-iodo-1-carbomethoxycubane (1) can be replaced by mesyloxy, toxyloxy and chloro by oxidative displacement with C6H5I(OH)OMs, C6H5I(OH)OTs and C6H5ICl2, respectively.Similarly, the iodo group in the homocubyl compound 4-iodo-1-bromopenta
FUNCTIONALIZED CUBANES. OXIDATIVE DISPLACEMENT UPON METHYL-4-IODOCUBANE CARBOXYLATE USING HYPERVALENT IODINE REAGENTS
Moriarty, Robert M.,Khosrowshahi, Jaffar S.,Penmasta, Raju
, p. 791 - 794 (2007/10/02)
Methyl 4-iodocubane carboxylate undergoes substitution via ligand exchange with the hypervalent reagents C6H5I(OH)OTs, C6H5I(OH)OMs and C6H5ICl2.
